This invention is in the field of synthetic organic chemistry. This invention pertains to simple, efficient and economic methods to produce xcex1-methylene-xcex3-butyrolactone from tetrahydro-3-furoic acid and xcex1-acetoxymethyl-xcex3-butyrolactone.
xcex1-Methylenelactones have been the subject of intensive synthetic studies. Specifically, the xcex1-methylene-xcex3-butyrolactone group is an important structural feature of many sesquiterpenes of biological importance. In addition, xcex1-methylene-xcex3-butyrolactone, or its hydrogenated product, 3-methyltetra-hydrofuran, are regarded as a potential key monomers in both homopolymers and copolymers. Currently the cost of xcex1-methylene-xcex3-butyrolactone is too high to warrant commercial production of its resulting polymers. Some of the current synthetic routes suffer from low yields, byproducts and expensive starting materials. In the instant invention, high yields of xcex1-methylene-xcex3-butyrolactone are obtained by an acid-catalyzed rearrangement of tetrahydro-3-furoic acid or base-catalyzed reaction of xcex1-acetoxymethyl-xcex3-butyrolactone.
An early synthesis of xcex1-methylene-xcex3-butyrolactone involved two steps (Martin et al., J. Chem. Soc. D 1:27 (1970)). The first is carboxylation of xcex3-butyrolactone with methyl methoxymagnesium carbonate (Stiles"" reagent) to produce the acid. Next, the acid is briefly treated with a mixture of aqueous formaldehyde and diethylamine, followed by a separate treatment of the crude product with sodium acetate in acetic acid. The first step requires 6-7 hours and affords almost quantitative yields, whereas the second step can be accomplished in less than 30 minutes but with yields of only 50%.
Murray et al. (Synthesis 1:35-38 (1985); see also U.S. Pat No. 5,166,357) disclose a route to xcex1-methylene-xcex3-butyrolactone that also involves a two-step sequence consisting of the reaction of xcex3-butyrolactone with ethyl formate in the presence of base, followed by refluxing the resulting xcex1-formyl-xcex3-butyrolactone sodium salt under nitrogen with paraformaldehyde in tetrahydrofuran. Distillation affords the desired xcex1-methylene-xcex3-butyrolactone as a colorless oil. This reaction sequence can best be explained by formyl transfer from carbon to oxygen followed by elimination of carboxylate anion.
Essentially all approaches to xcex1-methylene-xcex3-butyrolactone are liquid-phase processes. One exception is the vapor-phase process described in JP 10120672. Production of xcex1-methylene-xcex3-butyrolactone comprises subjecting xcex3-butyrolactone or an alkyl-substituted xcex3-butyrolactone, in which one or more hydrogen atoms at the xcex2- or xcex3-position of the xcex3-butyrolactone are substituted with C1-C18 alkyl groups, to a gaseous phase catalytic reaction using a raw material gas containing formaldehyde or its derivative in the presence of a catalyst. Molecular oxygen is preferably added to the raw material gas and the catalyst is preferably silica alumina catalyst. Specifically, a gaseous mixture of xcex3-butyrolactone, formaldehyde, water, nitrogen and oxygen was passed through a reactor packed with Wakogel C-200, pretreated with an aqueous potassium hydroxide solution and heating, at 330xc2x0 C., to afford xcex1-methylene-xcex3-butyrolactone at a conversion of 35.5% and a selectivity of 46.9%.
Although the above methods for the production of xcex1-methylene-xcex3-butyrolactone are useful, they are time consuming and are multipart processes. Therefore, the problem to be solved is to find a simple and efficient method to produce xcex1-methylene-xcex3-butyrolactone. The present methods represent an advance in the art by offering processes that are a single or double step with high yields and good selectivity.
The present invention provides a process for the preparation of xcex1-methylene-xcex3-butyrolactone comprising heating a mixture of a furoic acid selected from the group consisting of tetrahydro-3-furoic acid and esters of tetrahydro-3-furoic acid, and a strong acid catalyst under conditions whereby xcex1-methylene-xcex3-butyrolactone is formed and optionally recovering the xcex1-methylene-xcex3-butyrolactone. Typically the acid catalyst is selected from the group consisting of fluorosulfonic acid, trifluoromethanesulfonic acid, sulfuric acid, benzenesulfonic acid, toluenesulfonic acid and phosphoric acid.
In an alternate embodiment the invention provides a process for preparing xcex1-acetoxymethyl-xcex3-butyrolactone comprising heating a mixture of a furoic acid selected from the group consisting of tetrahydro-3-furoic acid and esters of tetrahydro-3-furoic acid, with acetic anhydride and a strong acid catalyst under conditions wherein xcex1-acetoxymethyl-xcex3-butyrolactone is formed and optionally recovering the xcex1-acetoxymethyl-xcex3-butyrolactone.
In another embodiment the present invention provides a process for preparing xcex1-methylene-xcex3-butyrolactone comprising heating a mixture of a gaseous furoic acid selected from the group consisting of tetrahydro-3-furoic acid and esters of tetrahydro-3-furoic acid and a gas phase base catalyst under conditions whereby xcex1-methylene-xcex3-butyrolactone is formed and optionally recovering the xcex1-methylene-xcex3-butyrolactone. Gas phase catalysts may be supported on suitable supports such as silica for example.
The invention additionally provides a novel composition of xcex1-acetoxy-methyl-xcex3-butyrolactone according to the formula 
Another embodiment of the invention relates to a process for preparing xcex1-methylene-xcex3-butyrolactone comprising heating a mixture of xcex1-acetoxymethyl-xcex3-butyrolactone and base catalyst under conditions whereby xcex1-methylene-xcex3-butyrolactone is formed and optionally recovering the xcex1-methylene-xcex3-butyrolactone. Within the context of this embodiment the base catalyst may be any base which forms an acetate when reacted with acetic acid and is typically defined according to the formula, M(acetate)x; where x is an integer selected from the group consisting of 1 and 2; and M is a cation of charge +x selected from the group consisting of Li+, Na+, K+, Rb+, Cs+, Mg++, Ca++, Sr++, Ba++, (CH3)4N+, (C2H5)4N+, (CH3)4P+, (C2H5)4P+ and 1-ethyl-3-methylimidazolium cation.
The invention additionally provides a process for preparing xcex1-methylene-xcex3-butyrolactone comprising: (a) combining a furoic acid selected from the group consisting of tetrahydro-3-furoic acid and an ester of tetrahydro-3-furoic acid with an acid anhydride and a strong acid catalyst under conditions whereby a xcex1-carboxylatomethyl-xcex3-butyrolactone is formed; (b) heating the product of step (a) under conditions whereby xcex1-methylene-xcex3-butyrolactone is formed; and (c) optionally recovering the xcex1-methylene-xcex3-butyrolactone. Typically the production of xcex1-carboxylatomethyl-xcex3-butyrolactone will occur at temperatures of about 20xc2x0 C. to about 200xc2x0 C. whereas the heating step will occur at temperatures of about 100xc2x0 C. to about 400xc2x0 C. Optionally abase catalyst may be added to the product of step (a) to effect the conversion of o-carboxylatomethyl-xcex3-butyrolactone to xcex1-methylene-xcex3-butyrolactone. Under these conditions the temperature required for conversion is less, and will range from about 40xc2x0 C. to about 200xc2x0 C. Within the context of this embodiment the base catalyst may be defined according to the formula, M(carboxylate)x where x is an integer selected from the group consisting of 1 and 2; and M is a cation of charge +x chosen from the group consisting of Li+, Na+, K+, Rb+, Cs+, Mg++, Ca++, Sr++, Ba++, (CH3)4N+, (C2H5)4N+, (CH3)4P+, (C2H5)4P+ and 1-ethyl-3-methylimidazolium cation; and carboxylate is selected from the group consisting of formate, acetate, propionate, benzoate, phthalate, poly(acrylate), succinate, monomethylsuccinate, 2,2xe2x80x2-dimethylsuccinate and 2,3-dimethylsuccinate.
xcex1-Methylene-xcex3-butyrolactone is useful as a key monomer in both homopolymers and copolymers. The instant invention pertains to a process for making xcex1-methylene-xcex3-butyrolactone by acid-catalyzed rearrangement of tetrahydro-3-furoic acid (Scheme I). In an alternate embodiment, when tetrahydro-3-furoic acid or esters of tetrahydro-3-furoic acid are treated with acetic anhydride and an acid catalyst, xcex1-acetoxymethyl-xcex3-butyrolactone is produced in high yield (Scheme II). Under either basic conditions, or high temperature (100xc2x0 C.-400xc2x0 C.) xcex1-acetoxymethyl-xcex3-butyrolactone can readily form xcex1-methylene-xcex3-butyrolactone by the elimination of acetic acid. Acid anhydrides other than acetic acid similarly can be used to form xcex1-methylene-xcex3-butyrolactone within the scope of this embodiment. These reactions provide xcex1-methylene-xcex3-butyrolactone by two novel routes which do not require butyrolactone or formaldehyde. 
Additionally the invention provides a novel compound, xcex1-acetoxymethyl-xcex3-butyrolactone which may serve as an intermediate or starting material for the production of xcex1-methylene-xcex3-butyrolactone (Scheme II) and is potentially useful in its own right as pre-polymer or polymer additive.
In the context of this disclosure, a number of terms and abbreviations shall be utilized for interpretation of the specification and the claims. The following definitions are provided.
xe2x80x9cNuclear magnetic resonancexe2x80x9d is abbreviated NMR. xe2x80x9cxcex1-methylene-xcex3-butyrolactonexe2x80x9d is abbreviated MBL xe2x80x9cxcex1-acetoxymethyl-xcex3-butyrolactonexe2x80x9d is abbreviated AMB
As used herein the term xe2x80x9ca xcex1-carboxylatomethyl-xcex3-butyrolactonexe2x80x9d means a compound having the structure: 
wherein RC(xe2x95x90O)O is a carboxylato group, for example if Rxe2x95x90CH3 then RC(xe2x95x90O)O is acetate.
As used herein the term xe2x80x9cstrong acid catalystxe2x80x9d means any Bronstead acid with a pKa less than 1, capable of catalyzing the conversion of tetrahydro-3-furoic acid or esters of tetrahydro-3-furoic acid to either AMB or MBL under suitable conditions.
The term xe2x80x9cbase or basic catalystxe2x80x9d or xe2x80x9cstrong base or basic catalystxe2x80x9d will refer to a basic catalyst useful in a low temperature, non-gas phase process for the production of xcex1-methylene-xcex3-butyrolactone. These catalysts are typically acetates or carboxylates.
The term xe2x80x9cgas phase base catalystxe2x80x9d refers to a basic catalyst used in a gas phase process for the production of xcex1-methylene-xcex3-butyrolactone.
The term xe2x80x9cfuroic acidxe2x80x9d as used herein will refer to the substituted furoic acids tetrahydro-3-furoic acid and esters of tetrahydro-3-furoic acid.
Furoic Acids
Furoic acids are useful as starting materials in the present invention, particularly tetrahydro-3-furoic acid and esters of tetrahydro-3-furoic acid. Suitable esters of tetrahydro-3-furoic acid include but are not limited to methyl tetrahydro-3-furoate, ethyl tetrahydro-3-furoate, propyl tetrahydro-3-furoate, butyl tetrahydro-3-furoate, and phenyl tetrahydro-3-furoate. The furoic acid may be provided in any state including solid, liquid or gaseous form, depending on the requirements of the reaction.
Acid Catalyst
The present invention provides an acidic catalyst for the conversion of tetrahydro-3-furoic acid to xcex1-methylene-xcex3-butyrolactone or xcex1-acetoxymethyl-xcex3-butyrolactone. Such catalysts are common and well known in the art. Suitable in the present invention are any Bronstead acids with a pKa less than 1, capable of catalyzing the conversion of tetrahydro-3-furoic acid or esters of tetrahydro-3-furoic acid to either AMB or MBL. For example suitable acids will include but are not limited to fluorosulfonic acid, trifluoromethanesulfonic acid, Nafion(copyright) perfluorocarbon sulfonic acid membrane, sulfuric acid, benzenesulfonic acid, toluenesulfonic acid and phosphoric acid. These acids may be used independently or jointly. A particularly useful acid catalyst is trifluoromethanesulfonic acid.
The amount of time required for complete conversion of the furoic acid starting material to product will vary with contact temperature. The temperature of the reaction for the conversion of tetrahydro-3-furoic acid to xcex1-methylene-xcex3-butyrolactone can range from about 20xc2x0 C. to about 400xc2x0 C., where a range of about 100xc2x0 C. to about 200xc2x0 C. is particularly suitable. The temperature of the reaction for the conversion of tetrahydro-3-furoic acid to xcex1-acetoxymethyl-xcex3-butyrolactone can range from about 20xc2x0 C. to about 200xc2x0 C., where a range of about 50xc2x0 C. to about 120xc2x0 C. is particularly suitable. Reaction times may vary from about 30 minutes under high temperature conditions to about 100 hours under less favorable temperature conditions. Typically reactions may be completed in about 1 to about 24 hours.
Base Catalyst and Gas Phase Base Catalyst
The present invention provides a basic catalyst for the conversion of xcex1-acetoxymethyl-xcex3-butyrolactone, where acetic anhydride is an element of the reaction mixture, to xcex1-methylene-xcex3-butyrolactone. Such catalysts are common and well known in the art. Where acetic anhydride is an element of the reaction mixture a suitable base catalyst is any base that will form an acetate upon reacting with acetic acid. In this context, suitable bases will be defined by the formula M(acetate)x, where x is 1 or 2; M is a cation of charge +x, including but not limited to Li+, Na+, K+, Rb+, Cs+, Mg++, Ca++, Sr++, Ba++, (CH3)4N+, (C2H5)4N+, (CH3)4P+, (C2H5)4P+ and 1-ethyl-3-methylimidazolium cations. Particularly suitable in the present invention are the bases tetramethylammonium acetate and 1-ethyl-3-methylimidazolium acetate.
Alternatively, where any acid anhydride is an element of the reaction the base will be defined by the formula, M(carboxylate)x, where x is 1 or 2; M is a cation of charge +x including, but not limited to Li+, Na+, K+, Rb+, Cs+, Mg++, Ca++, Sr++, Ba++, (CH3)4N+, (C2H5)4N+, (CH3)4P+, (C2H5)4P+ and 1-ethyl-3-methylimidazolium cations; and the carboxylate may include formate, acetate, propionate, benzoate, phthalate, poly(acrylate), succinate, monomethyl-succinate, 2,2xe2x80x2-dimethylsuccinate and 2,3-dimethylsuccinate. It will be appreciated that any of the aforementioned bases may be used independently or jointly to effect the desired conversion.
As with the acid catalyzed reactions the amount of time required for complete conversion of acetoxymethyl-xcex3-butyrolactone to xcex1-methylene-xcex3-butyrolactone will vary with contact temperature. Typically temperature of the reaction can range from about 40xc2x0 C. to about 200xc2x0 C., where a range of about 60xc2x0 C. to about 140xc2x0 C. is particularly suitable.
In an alternate embodiment the present invention provides a gas phase process for the production of xcex1-methylene-xcex3-butyrolactone where a gaseous furoic acid is passed over a gas phase base catalyst at high temperature. In this embodiment suitable temperatures may range from about 100xc2x0 C. to about 600xc2x0 C. Suitable gas phase base catalysts may include but are not limited to magnesium oxide, calcium oxide, strontium oxide, barium oxide, magnesium hydroxide, calcium hydroxide, cadmium oxide, potassium hydroxide, strontium hydroxide, rubidium oxide, sodium hydroxide, lithium hydroxide and barium hydroxide. The gas phase catalysts may be used individually or in any combination, or may optionally be supported on a variety of supports. Suitable supports are well known in the art and may include, but are not limited to silica, titania, zirconia, alumina and various zeolites.
Acid Anhydride
The present invention provides an acid anhydride for the conversion of tetrahydro-3-furoic acid or esters of tetrahydro-3-furoic acid to xe2x80x9cxcex1-carboxylato-methyl-xcex3-butyrolactonexe2x80x9d. When the acid anhydride is acetic anhydride, the product is xcex1-acetoxymethyl-xcex3-butyrolactone. From this point the xcex1-carboxylato-methyl-xcex3-butyrolactone or xcex1-acetoxymethyl-xcex3-butyrolactone may be converted to end product either via the use of a base catalyst (discussed above) or by thermolysis at temperatures in the range of 100xc2x0 C. to 400xc2x0 C. Such anhydrides are common and well known in the art. In the context of the present invention, suitable anhydrides will include but are not limited to acetic anhydride, formic-acetic anhydride, propionic anhydride, benzoic anhydride, phthalic anhydride, anhydrides of poly(acrylic acid), succinic anhydride, monomethylsuccinic anhydride, 2,2xe2x80x2-dimethylsuccinic anhydride and 2,3-dimethylsuccinic anhydride. The preferred acid anhydride is acetic anhydride. Phthalic anhydride, anhydrides of poly(acrylic acid), succinic anhydride, monomethylsuccinic anhydride, 2,2xe2x80x2-dimethylsuccinic anhydride and 2,3-dimethylsuccinic anhydride all offer the possibly advantageous feature that the corresponding acids, which form during the course of the reaction, can be thermally dehydrated to recover the anhydride.
The skilled person will recognize that optimization of any catalytic conversion will involve determination of a specific ratio of catalyst to starting material, and methods for determining such ratios are well established in the art. In the context of the present invention for the production of MBL the ratio of furoic acid reactant to the acid catalyst will range from about 1:1,000 to about 10,000:1 w/w where a ratio of about 1000:1 w/w is suitable.
Similarly, where an acid anhydride is an element of the reaction the ratio of the furoic acid starting material and acid anhydride may range from about 10:1 to about 1:10,000 w/w where a range of about 1:1 to about 1:10,000 w/w is suitable.
Segregated Acid Catalyst and Base Catalyst
In one embodiment of the invention the conversion of tetrahydro-3-furoic acid to ABM or MBL was accomplished in a common vessel under conditions whereby the acid and base catalysts were segregated. Ordinarily, combining a strong acid catalyst with a basic catalyst results in immediate neutralization and loss of catalytic activity. However, this difficulty may be overcome if the acid catalyst and basic catalyst are separately maintained on segregated supports. In this fashion each catalyst maintains its individual catalytic activity without complete neutralization.
In the context of the present invention, Nafion(copyright) perfluorocarbon sulfonic acid membrane was used as the requisite acid catalyst and acetate-loaded anion exchange resin (for example, Dowex(copyright) 1X8-100 beads) was used as the requisite basic catalyst in a single vessel conversion of tetrahydro-3-furoic acid to both ABM and MBL. Good conversions were observed for both products as indicated in Example 12.
Reaction Conditions and Processes
The present method lends itself to either batch or continuous processes. A continuous process employs a pipeline reactor for the tetrahydro-3-furoic acid to xcex1-methylene-xcex3-butyrolactone conversion. Liquid tetrahydro-3-furoic acid is fed into a pipe containing a catalyst bed where the reaction occurs to make xcex1-methylene-xcex3-butyrolactone. Any off-gases are vented out the end of the pipeline and the xcex1-methylene-xcex3-butyrolactone product falls out as a liquid. If needed, the mixture can be fed into the pipeline again to increase the overall conversion to xcex1-methylene-xcex3-butyrolactone.
Alternatively, the reaction can run under continuous flow conditions, where water is constantly removed from the reaction medium and neither starting tetrahydro-3-furoic acid nor product xcex1-methylene-xcex3-butyrolactone is allowed to be present in concentration great enough for rapid polymerization.
Recovery Methods
xcex1-methylene-xcex3-butyrolactone, may be recovered using techniques common to the art. For example, when allowed to cool the xcex1-methylene-xcex3-butyrolactone reaction mixture, forms a viscous, clear mass. Alternatively, when heated under vacuum, the xcex1-methylene-xcex3-butyrolactone mixture can be distilled directly from the reaction mixture. Additionally, the reaction mixture can be dissolved in water, adjusted to pH=4 with 6N HCl, then distilled. Similarly, the separation of xcex1-methylene-xcex3-butyrolactone from byproducts can be accomplished using vacuum distillation with a spinning band column. Another method to recover the desired product is to polymerize xcex1-methylene-xcex3-butyrolactone using standard free-radical polymerization, isolate the polymer by precipitation from methanol, then thermally depolymerize back to xcex1-methylene-xcex3-butyrolactone by heating under vacuum. Finally, xcex1-methylene-xcex3-butyrolactone may also be separated from byproducts by melt crystallization.
xcex1-Acetoxymethyl-xcex3-butyrolactone may be recovered by distillation methods comparable to distillation methods discussed above for the isolation of MBL. xcex1-Acetoxymethyl-xcex3-butyrolactone is relatively stable and has been distilled in vacuum at temperatures less than about 140xc2x0 C. to afford a colorless oil which crystallizes upon cooling and standing to a white crystalline compound, but it can thermolyze to xcex1-methylene-xcex3-butyrolactone and darkly-colored residue when heated much above that temperature. Given that pure xcex1-acetoxymethyl-xcex3-butyrolactone crystallizes at room temperature, care must be taken during its distillation to avoid plugging the condenser. The molecular structure of xcex1-acetoxymethyl-xcex3-butyrolactone as determined by single crystal X-ray diffraction revealed no extraordinary features.
The identification of AMB was confirmed after purification by NMR and revealed the following spectral data:
1H NMR (500 MHz, CD2Cl2) xcex42.06 (s, 3H), 2.2 (m, 1H), 2.4 (m, 1H), 2.9 (m, 1H), 4.25 (m, 2H), 4.38 (m, 2H); 13C NMR (125 MHz, CD2Cl2) xcex421.1, 26.3, 39.8, 63.1, 67.4, 171.1, 177.1. 1H NMR spectra are reported in ppm downfield from tetramethylsilane; s=singlet and m=multiplet. Anal. Calcd. for C7H10O4: C, 53.16%; H, 6.37. Found C, 53.12; H, 6.46.